We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infecte... more We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Active toxoplasmosis was suspected due to persistent lymphadenitis with specific IgM, IgA, IgE antibodies. Prenatal diagnosis based on amniocentesis and fetal blood sampling at 24 weeks' amenorrhoea was positive on amniotic fluid, and fetal infection was confirmed after termination. In our opinion such cases need the same monitoring as when seroconversion occurs during the first trimester. A pregnancy-free interval of six to nine months is recommended after proven patent toxoplasmosis seroconversion.
The authors have compared the diagnostic value in congenital toxoplasmosis of two recently develo... more The authors have compared the diagnostic value in congenital toxoplasmosis of two recently developed immunological techniques, Enzyme Linked immunofiltration Assay (ELIFA) and IgM-immunocapture (or immunosorbent agglutination assay). The study involved 50 children suffering from congenital toxoplasmosis and 300 unscathed control children, whose mothers suffered from toxoplasmosis during their pregnancies. The ELIFA technique showed a sensitivity of 74 p. cent at the end of the first month after birth (day 30) and 84 p. cent after two months (day 60), whereas the IgM-immunocapture technique gave a sensitivity of 64 p. cent at day 30 and 70 p. cent at day 60. Both methods were at least 95 p. cent specific. The two techniques seem to be complementary to each other, and their association allowed the diagnosis to be confirmed in 80 p. cent of cases at day 30 and in 90 p. cent of cases at day 60. A serum sample taken on the tenth day after birth (day 10) was important both to eliminate th...
Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting ... more Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting results. In this study, co-counterimmunoelectrodiffusion was used to detect antimannan antibodies specific of components of the Candida membrane. Study patients were divided into two groups according to whether their history for Candida infection was negative (population A, n = 102) or positive (population B). Different antigen levels were used in order to differentiate low and high antimannan antibody levels. Among the 102 sera in population A, 42 were positive for antimannan antibodies; the antimannan antibody titer was low in 40 cases and high in 2 cases. In population B (53 patients), antimannan antibodies were found in 97 of the 98 sera studied; titers were high in 95 cases. Use of an antigen level that detects only high titers of antimannan antibodies thus provides a sensitive and specific tool for the diagnosis of deep candidiasis. The simplicity and rapidity of this test are part...
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is ... more Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is affected by toxoplasmosis is to treat it as soon as the diagnosis has been made. The authors who already have experience of using pyrimethamine with sulfadoxoine (Fansidar) in the post-natal treatment of congenital infection, thought after reviewing the literature that this association of drugs would be harmless if applied during pregnancy. The principal risk that arises in the fetus is the teratogenicity of each of the components of pyrimethamine and sulfadoxine and also their associations. In animals pyrimethamine can increase the frequency of cleft palates probably because of its antifolinic action but there is no formal proof that it is teratogenic in human beings. Furthermore, the theoretical risk of karnicerus in the new born using the Sulfonamide has not been demonstrated. In the mother the main but rare risk (1 in 75,000) seems to be for the production of severe skin lesions such...
The use of International Units per ml (IU/ml) to express antitoxoplasmic IgG antibody titers in t... more The use of International Units per ml (IU/ml) to express antitoxoplasmic IgG antibody titers in the various diagnostic systems presently proposed, is misleading owing to discrepancies in the values found from one test to the other for a given serum. The authors compared the results of high sensitivity direct agglutination (HSDA) to those of indirect immunofluorescence (IIF) in two studies, systematic and longitudinal, dealing with 158 sera stratified for values ranging from 102,400 to 5 IU/ml. Discordances between the methods, which are greater for high values, prompt the use of low-titer sera for standardization. From the systematic study, a correlation table was established and proposed to convert the HSDA results into the theoretical corrected values close to those that would be obtained by IIF. Although this may be of interest in maintaining a coherent language, this table has its limits, particularly in acute episodes where the various antibody kinetics vary and amplify further...
Enzyme‐linked immunofiltration assay (ELIFA) for labeling transferred proteins is an interesting ... more Enzyme‐linked immunofiltration assay (ELIFA) for labeling transferred proteins is an interesting and powerful technique for the rapid specific detection (15 min) of proteins immobilized on nitrocellulose or nylon membranes (0.20 and 0.45 μm). ELIFA does not require fastidious handling of the membranes. Saturation, specific labeling and washing procedures are achieved by filtration, controlled by a monitoring unit which regulates the flow rate and ensures excellent specificity, repetition and reproducibility. The recycling by closed circuit or by repetetive inversion of the flow direction offers the advantage of reducing the volumes of expensive reagents while simultaneously increasing the sensitivity of the technique. The detection limit is at least as low as 1–5 ng using directly or indirectly enzymatically labelled probes. ELIFA may be extended to the identification of glycoproteins using specific ligands such as lectins or to the immunocapture of an antigen using specific antibod...
lsotypic characterization of anti-Toxoplasma gondii antibodies in 18 cases of conge n i tal toxo ... more lsotypic characterization of anti-Toxoplasma gondii antibodies in 18 cases of conge n i tal toxo p I asm i c c h or i o ret i n it i s
Presse médicale (Paris, France : 1983), Jan 3, 1990
The authors report 2 cases of congenital toxoplasmosis fortuitously diagnosed in 2 newborn infant... more The authors report 2 cases of congenital toxoplasmosis fortuitously diagnosed in 2 newborn infants aged 12 and 35 days respectively whose mothers had no anti-Toxoplasma antibodies detectable at the time of birth. These cases prompted us to carry out, over an 18 months' period, a systematic postnatal control of all pregnant women who were still seronegative at the time of delivery. This enabled us to detect 4 cases of perinatal maternal infection with Toxoplasma contamination in 2 neonates. In view of these results, and in order not to miss any maternal infection at the very end of pregnancy, it seems advisable to complete the control of seronegative women by taking a last blood sample about 30 days after they have given birth.
BackgroundMicrosporidiosis has been largely reported in patients with acquired immunodeficiency s... more BackgroundMicrosporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients.MethodsThrough the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France.ResultsWe identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5‐83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1‐18.9) years post‐transplant. Median duration of diarrhea before diagnosis was 22 days (12‐45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients rec...
To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects... more To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detect...
An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) ... more An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) in sera from adults with acute acquired infection or reactivation and from babies with congenital toxoplasmosis. The components of this assay were monoclonal antibody to human IgE, samples from patients, and T. gondii tachyzoites treated with Formalin. When T. gondii-specific IgE antibodies were present, visually detectable agglutination occurred. Sera, umbilical cord blood, fetal blood, cerebrospinal fluid, and amniotic fluid were tested by this method. Specific IgE antibodies were detected in sera from 25 (86%) of 29 adults who developed specific IgG antibody during pregnancy or had specific IgA and IgM antibodies. Specific IgE was present early during infection, at the time that IgM antibodies were present, and slightly preceding the presence of specific IgA antibodies. In 23 patients tested serially, IgE antibodies never persisted for longer than 4 months. No nonspecific anti-T. gond...
Alveolar echinococcosis (AE) is a parasitic disease, due to Echinococcus multilocularis. Often co... more Alveolar echinococcosis (AE) is a parasitic disease, due to Echinococcus multilocularis. Often compared to liver cancer, it develops by infiltration from its primary site to the surrounding tissue, and can then metastasize to other organs. Detection of circulating cell-free DNA (ccfDNA) is a useful analytical tool in oncology, for diagnosis, prognosis, and therapy monitoring. This study sought to investigate the presence of ccfDNA in patients with AE, and its potential usefulness for the evaluation of treatment efficiency. To achieve these aims, a quantitative PCR and a droplet digital PCR were developed to detect E. multilocularis ccfDNA. An AE animal model identified, for the first time, the presence of large quantities of ccfDNA. Samples from patients with AE (n = 31) were then analyzed twice, at diagnosis, and after three months of chemotherapy: about 25% were positive, almost always with very low concentrations of ccfDNA. These results confirmed that E. multilocularis produces ccfDNA, as solid tumors do, but detection may not yet be sufficient for AE diagnosis nor for the evaluation of treatment efficiency, due to the low levels of ccfDNA detected in patient serum.
We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infecte... more We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Active toxoplasmosis was suspected due to persistent lymphadenitis with specific IgM, IgA, IgE antibodies. Prenatal diagnosis based on amniocentesis and fetal blood sampling at 24 weeks' amenorrhoea was positive on amniotic fluid, and fetal infection was confirmed after termination. In our opinion such cases need the same monitoring as when seroconversion occurs during the first trimester. A pregnancy-free interval of six to nine months is recommended after proven patent toxoplasmosis seroconversion.
The authors have compared the diagnostic value in congenital toxoplasmosis of two recently develo... more The authors have compared the diagnostic value in congenital toxoplasmosis of two recently developed immunological techniques, Enzyme Linked immunofiltration Assay (ELIFA) and IgM-immunocapture (or immunosorbent agglutination assay). The study involved 50 children suffering from congenital toxoplasmosis and 300 unscathed control children, whose mothers suffered from toxoplasmosis during their pregnancies. The ELIFA technique showed a sensitivity of 74 p. cent at the end of the first month after birth (day 30) and 84 p. cent after two months (day 60), whereas the IgM-immunocapture technique gave a sensitivity of 64 p. cent at day 30 and 70 p. cent at day 60. Both methods were at least 95 p. cent specific. The two techniques seem to be complementary to each other, and their association allowed the diagnosis to be confirmed in 80 p. cent of cases at day 30 and in 90 p. cent of cases at day 60. A serum sample taken on the tenth day after birth (day 10) was important both to eliminate th...
Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting ... more Several groups have evaluated detection of antibodies against Candida, with somewhat conflicting results. In this study, co-counterimmunoelectrodiffusion was used to detect antimannan antibodies specific of components of the Candida membrane. Study patients were divided into two groups according to whether their history for Candida infection was negative (population A, n = 102) or positive (population B). Different antigen levels were used in order to differentiate low and high antimannan antibody levels. Among the 102 sera in population A, 42 were positive for antimannan antibodies; the antimannan antibody titer was low in 40 cases and high in 2 cases. In population B (53 patients), antimannan antibodies were found in 97 of the 98 sera studied; titers were high in 95 cases. Use of an antigen level that detects only high titers of antimannan antibodies thus provides a sensitive and specific tool for the diagnosis of deep candidiasis. The simplicity and rapidity of this test are part...
Journal de Gynécologie Obstétrique et Biologie de la Reproduction
Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is ... more Some of the alternative treatments to avoid termination of pregnancy in cases where the fetus is affected by toxoplasmosis is to treat it as soon as the diagnosis has been made. The authors who already have experience of using pyrimethamine with sulfadoxoine (Fansidar) in the post-natal treatment of congenital infection, thought after reviewing the literature that this association of drugs would be harmless if applied during pregnancy. The principal risk that arises in the fetus is the teratogenicity of each of the components of pyrimethamine and sulfadoxine and also their associations. In animals pyrimethamine can increase the frequency of cleft palates probably because of its antifolinic action but there is no formal proof that it is teratogenic in human beings. Furthermore, the theoretical risk of karnicerus in the new born using the Sulfonamide has not been demonstrated. In the mother the main but rare risk (1 in 75,000) seems to be for the production of severe skin lesions such...
The use of International Units per ml (IU/ml) to express antitoxoplasmic IgG antibody titers in t... more The use of International Units per ml (IU/ml) to express antitoxoplasmic IgG antibody titers in the various diagnostic systems presently proposed, is misleading owing to discrepancies in the values found from one test to the other for a given serum. The authors compared the results of high sensitivity direct agglutination (HSDA) to those of indirect immunofluorescence (IIF) in two studies, systematic and longitudinal, dealing with 158 sera stratified for values ranging from 102,400 to 5 IU/ml. Discordances between the methods, which are greater for high values, prompt the use of low-titer sera for standardization. From the systematic study, a correlation table was established and proposed to convert the HSDA results into the theoretical corrected values close to those that would be obtained by IIF. Although this may be of interest in maintaining a coherent language, this table has its limits, particularly in acute episodes where the various antibody kinetics vary and amplify further...
Enzyme‐linked immunofiltration assay (ELIFA) for labeling transferred proteins is an interesting ... more Enzyme‐linked immunofiltration assay (ELIFA) for labeling transferred proteins is an interesting and powerful technique for the rapid specific detection (15 min) of proteins immobilized on nitrocellulose or nylon membranes (0.20 and 0.45 μm). ELIFA does not require fastidious handling of the membranes. Saturation, specific labeling and washing procedures are achieved by filtration, controlled by a monitoring unit which regulates the flow rate and ensures excellent specificity, repetition and reproducibility. The recycling by closed circuit or by repetetive inversion of the flow direction offers the advantage of reducing the volumes of expensive reagents while simultaneously increasing the sensitivity of the technique. The detection limit is at least as low as 1–5 ng using directly or indirectly enzymatically labelled probes. ELIFA may be extended to the identification of glycoproteins using specific ligands such as lectins or to the immunocapture of an antigen using specific antibod...
lsotypic characterization of anti-Toxoplasma gondii antibodies in 18 cases of conge n i tal toxo ... more lsotypic characterization of anti-Toxoplasma gondii antibodies in 18 cases of conge n i tal toxo p I asm i c c h or i o ret i n it i s
Presse médicale (Paris, France : 1983), Jan 3, 1990
The authors report 2 cases of congenital toxoplasmosis fortuitously diagnosed in 2 newborn infant... more The authors report 2 cases of congenital toxoplasmosis fortuitously diagnosed in 2 newborn infants aged 12 and 35 days respectively whose mothers had no anti-Toxoplasma antibodies detectable at the time of birth. These cases prompted us to carry out, over an 18 months' period, a systematic postnatal control of all pregnant women who were still seronegative at the time of delivery. This enabled us to detect 4 cases of perinatal maternal infection with Toxoplasma contamination in 2 neonates. In view of these results, and in order not to miss any maternal infection at the very end of pregnancy, it seems advisable to complete the control of seronegative women by taking a last blood sample about 30 days after they have given birth.
BackgroundMicrosporidiosis has been largely reported in patients with acquired immunodeficiency s... more BackgroundMicrosporidiosis has been largely reported in patients with acquired immunodeficiency syndrome, but emerged as a cause of persistent diarrhea in solid organ transplant patients.MethodsThrough the French Microsporidiosis Network and the Groupe français de recherche en greffe de foie, we collected all microsporidiosis cases identified in liver transplant patients between 1995 and 2020 in France.ResultsWe identified 24 liver transplant recipients with microsporidiosis. Sex ratio was balanced and median age was 58.8 (3.5‐83.5) years (there were 4 children). Microsporidiosis occurred at a median time of 3.9 (0.1‐18.9) years post‐transplant. Median duration of diarrhea before diagnosis was 22 days (12‐45). Therapeutic care included immunosuppressive therapy changes in 20 patients, as follows: stop cyclosporine or tacrolimus (n = 2), dose reduction of cyclosporine or tacrolimus (n = 12), stop MMF (n = 5), and dose reduction of corticosteroids (n = 1). In addition, 15 patients rec...
To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects... more To determine their prognostic and diagnostic values for toxoplasmosis in immunodepressed subjects, we assayed immunoglobulin A (IgA) and IgE antibodies by means of immunocapture (IC) tests, with revelation done by using a suspension of T. gondii (ICT). We also carried out a simultaneous analytical study of IgG antibodies on cellulose acetate membranes by using the comparative immunological profile method and an enzyme-linked immunofiltration assay (ELIFA). A total of 1,238 samples (serum, cerebrospinal fluid, and aqueous humor from 318 patients) were tested. IgA and IgE antibodies were detected in all heart, kidney, and liver transplant recipients with clinical manifestations of toxoplasmosis; IgA was detected in the aqueous humor of a patient with chorioretinitis. In patients with AIDS-related toxoplasmosis, including the cerebral form, IgA and IgE antibodies or a significant modification of ELIFA IgG values were observed in 38, 19, and 25% of patients, respectively. IgM was detect...
An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) ... more An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) in sera from adults with acute acquired infection or reactivation and from babies with congenital toxoplasmosis. The components of this assay were monoclonal antibody to human IgE, samples from patients, and T. gondii tachyzoites treated with Formalin. When T. gondii-specific IgE antibodies were present, visually detectable agglutination occurred. Sera, umbilical cord blood, fetal blood, cerebrospinal fluid, and amniotic fluid were tested by this method. Specific IgE antibodies were detected in sera from 25 (86%) of 29 adults who developed specific IgG antibody during pregnancy or had specific IgA and IgM antibodies. Specific IgE was present early during infection, at the time that IgM antibodies were present, and slightly preceding the presence of specific IgA antibodies. In 23 patients tested serially, IgE antibodies never persisted for longer than 4 months. No nonspecific anti-T. gond...
Alveolar echinococcosis (AE) is a parasitic disease, due to Echinococcus multilocularis. Often co... more Alveolar echinococcosis (AE) is a parasitic disease, due to Echinococcus multilocularis. Often compared to liver cancer, it develops by infiltration from its primary site to the surrounding tissue, and can then metastasize to other organs. Detection of circulating cell-free DNA (ccfDNA) is a useful analytical tool in oncology, for diagnosis, prognosis, and therapy monitoring. This study sought to investigate the presence of ccfDNA in patients with AE, and its potential usefulness for the evaluation of treatment efficiency. To achieve these aims, a quantitative PCR and a droplet digital PCR were developed to detect E. multilocularis ccfDNA. An AE animal model identified, for the first time, the presence of large quantities of ccfDNA. Samples from patients with AE (n = 31) were then analyzed twice, at diagnosis, and after three months of chemotherapy: about 25% were positive, almost always with very low concentrations of ccfDNA. These results confirmed that E. multilocularis produces ccfDNA, as solid tumors do, but detection may not yet be sufficient for AE diagnosis nor for the evaluation of treatment efficiency, due to the low levels of ccfDNA detected in patient serum.
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